1. Field of Invention
This invention relates to diaryl thiophenes, their preparation, pharmaceutical compositions containing them and methods of using them to treat inflammation and/or pain in mammals. More particularly, this invention relates to antiinflammatory and/or analgesic 2,3-diaryl-5-silyl thiophenes.
2. Prior Art
There is a continuing need for safe and effective antiinflammatory agents. Inflammation is a disease process characterized by redness, fever, swelling, and pain. Arthritis, in its various forms, is the most prevalent, chronic, and severe of the inflammatory diseases. Traumatic injury and infection also involve inflammation, and antiinflammatory drugs are often used in their treatment. The usefulness of most commercial antiinflammatories is limited because of toxicity and adverse side-effects. Many produce gastric irritation and other effects, such as changes in blood cells and central nervous system. Adreno-cortical steroids produce gastric irritation and suppression of normal adrenal function.
The present invention results from efforts to develop new antiarthritic compounds with good antiinflammatory activity and minimal side effects that could be more effective in treating arthritis than presently available drugs.
In addition to antiinflammatory properties, some compounds of this invention have analgesic activity. This additional property is desirable in treatment of arthritis or related diseases; however, such compounds can be employed solely to alleviate pain.
A number of references including J. L. Melles and H. J. Becker, Rec. Trav. Chim., 72, 314 (1953) and S. Hauptmann and E. M. Werner, J. Prakt. Chem., 314, 499 (1972) describe the preparation of 2,3-diaryl thiophenes.
The use of the trialkylsilyl group to trap reactive carbanions and hence its introduction onto aromatic nuclei is well known in the chemical literature. Examples may be found in D. Habich and F. Effenberger, Synthesis, 841 (1979) and T. Kauffmann and A. Mitschker, Tet. Lett., 4039 (1973). The preparation of a 2-trimethylsilyl-5-aryl thiophene by the reaction of 5-lithio-2-trimethylsilyl thiophene with 1,3-dicyanotetrachlorobenzene is described in F. H. Pinkerton and S. F. Thames, J. Het. Chem., 9, 725 (1972).